​Mitochondrial DNA encodes a host of previously unrecognized novel peptides with important biological activities. These peptides serve as signals from this cellular organelle (that is responsible for respiration as well as cell death) to the parent cell and its nucleus, as well as the entire organism. This line of investigation, recently funded by a transformative-RO1 grant, has implications for multiple diseases associated with mitochondrial dysfunction, including Alzheimer¹s, Diabetes, and Cancer. The new small protein molecules, (MDPs or mitochondrial-derived peptides) may emerge in the future as potential therapeutics or diagnostic tools, and reshape our understanding of the function of the elusive organelle, the mitochondrion.